The number of comorbidities as an important cofactor to ASA class in predicting postoperative outcome: An international multicentre cohort study.

BACKGROUND: Multimorbidity is a growing burden in our ageing society and is associated with perioperative morbidity and mortality. Despite several modifications to the ASA physical status classification, multimorbidity as such is still not considered. Thus, the aim of this study was to quantify the burden of comorbidities in perioperative patients and to assess, independent of ASA class, its potential influence on perioperative outcome. METHODS: In a subpopulation of the prospective ClassIntra® validation study from eight international centres, type and severity of anaesthesia-relevant comorbidities were additionally extracted from electronic medical records for the current study. Patients from the validation study were of all ages, undergoing any type of in-hospital surgery and were followed up until 30 days postoperatively to assess perioperative outcomes. Primary endpoint was the number of comorbidities across ASA classes. The associated postoperative length of hospital stay (pLOS) and Comprehensive Complication Index (CCI®) were secondary endpoints. On a scale from 0 (no complication) to 100 (death) the CCI® measures the severity of postoperative morbidity as a weighted sum of all postoperative complications. RESULTS: Of 1421 enrolled patients, the mean number of comorbidities significantly increased from 1.5 in ASA I (95% CI, 1.1-1.9) to 10.5 in ASA IV (95% CI, 8.3-12.7) patients. Furthermore, independent of ASA class, postoperative complications measured by the CCI® increased per each comorbidity by 0.81 (95% CI, 0.40-1.23) and so did pLOS (geometric mean ratio, 1.03; 95% CI, 1.01-1.06). CONCLUSIONS: These data quantify the high prevalence of multimorbidity in the surgical population and show that the number of comorbidities is predictive of negative postoperative outcomes, independent of ASA class.

Pharmacokinetics-Based Pediatric Dose Evaluation and Optimization Using Saliva - A Case Study.

Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling in children is challenging, alternative PK sampling strategies are needed. In this case study we evaluated the suitability of saliva as alternative PK matrix to simplify studies in infants, investigating metamizole, an analgesic used off-label in infants. Six plasma and 6 saliva PK sample collections were scheduled after a single intravenous dose of 10 mg/kg metamizole. Plasma/saliva pharmacometric (PMX) modeling of the active metabolites 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA) was performed. Various reduced plasma sampling scenarios were evaluated by PMX simulations. Saliva and plasma samples from 25 children were included (age range, 5-70 months; weight range, 8.7-24.8 kg). Distribution of metamizole metabolites between plasma and saliva was without delay. Estimated mean (individual range) saliva/plasma fractions of 4-MAA and 4-AA were 0.32 (0.05-0.57) and 0.57 (0.25-0.70), respectively. Residual variability of 4-MAA (4-AA) in saliva was 47% (28%) versus 17% (11%) in plasma. A simplified sampling scenario with up to 6 saliva samples combined with 1 plasma sample was associated with similar PK parameter estimates as the full plasma sampling scenario. This case study with metamizole shows increased PK variability in saliva compared to plasma, compromising its suitability as single matrix for PK studies in infants. Nonetheless, rich saliva sampling can reduce the number of plasma samples required for PK characterization, thereby facilitating the conduct of PK studies to optimize dosing in pediatric patients.

A Comparison of Proximal and Tracheal Airway Pressures During Pressure Controlled Ventilation.

BACKGROUND: Airway pressure is usually measured by sensors placed in the ventilator or on the ventilator side of the endotracheal tube (ETT), at the Y-piece. These remote measurements serve as a surrogate for the tracheal or alveolar pressure. Tracheal pressure can only be predicted correctly by using a model that incorporates the pressure at the remote location, the flow through the ETT, and the resistance of the ETT if the latter is a predictable function of Y-piece flow. However, this is not consistently appropriate, and accuracy of prediction is hampered. METHODS: This in vitro study systematically examined the ventilator pressure in dependence of compliance of the respiratory system (CRS), inspiratory time, and expiratory time during pressure-controlled ventilation by using a small intratracheal pressure sensor and a mechanical lung simulator. Pressures were measured simultaneously at the ventilator outlet, at the Y-piece, and in the trachea during pressure-controlled ventilation with a peak inspiratory pressure of 20 cm H2O and a PEEP of 5 cm H2O while changing CRS (10, 30, 60, 90, and 100 mL/cm H2O) and varying inspiratory time and expiratory time. RESULTS: Tracheal pressures were always lower (maximum 8 cm H2O during inspiration) or higher (maximum 4 cm H2O during expiration) than the pressures measured proximal to the ETT if zero-flow conditions were not achieved at the end of the breathing cycles. CONCLUSIONS: Dependent on CRS and the breathing cycle, tracheal pressures deviated from those measured proximal to the ETT under non-zero-flow conditions. Intratracheal pressure and pressure curve dynamics can differ greatly from the ventilator pressure, depending on the ventilator setting and the CRS. The small pressure sensor may be used as a measurement method of tracheal pressure via integration onto an ETT.

Special Anaesthetic Considerations for Brain Tumour Surgery in Children.

Brain tumours are among the most common neoplasm in children. Therefore, paediatric anaesthesiologists face the challenge of neurosurgical interventions in all age groups. To minimize perioperative mortality and morbidity, a comprehensive understanding of age-dependent differences in anatomy and cerebrovascular physiology is a mandatory prerequisite. Advances in subspeciality training in paediatric neurosurgery and paediatric anaesthesia may improve clinical outcomes and advance communication between the teams.

Testing of pandemic ventilators under early and agile development.

Aiming to address clinical requirements subsequent to SARS-CoV-2-related pulmonary disease, multiple research groups and industry groups carried out intensive studies to develop pandemic ventilators (PDVs). In vitro testing to critically evaluate the specific performance of the developed apparatuses is an essential requirement. This study presents a test protocol which promotes a test-oriented, iterative, and agile assessment and consecutive development of such PDVs. It allows for fast identification of specific characteristics of each PDV in the individual test features. The test protocol includes an evaluation of the accuracy of control systems and instruments at changing parameters, the oxygen dynamics, and the response to trigger signals. The test environment is a mechanical lung, which allows reproducing various lung mechanics and to simulate active breathing cycles. A total of three PDVs that are under development were iteratively tested, with a Hamilton T1 as a reference. Continuous testing of the PDVs under development enables quick identification of critical application aspects that deserve further improved. Based on the present test protocol, the ventilators demonstrate a promising performance justifying continued development.

Developmental respiratory physiology.

Various developmental aspects of respiratory physiology put infants and young children at an increased risk of respiratory failure, which is associated with a higher rate of critical incidents during anesthesia. The immaturity of control of breathing in infants is reflected by prolonged central apneas and periodic breathing, and an increased risk of apneas after anesthesia. The physiology of the pediatric upper and lower airways is characterized by a higher flow resistance and airway collapsibility. The increased chest wall compliance and reduced gas exchange surface of the lungs reduce the pulmonary oxygen reserve vis-à-vis a higher metabolic oxygen demand, which causes more rapid oxygen desaturation when ventilation is compromised. This review describes the various developmental aspects of respiratory physiology and summarizes anesthetic implications.

Pain during Cast Wedging of Forearm Shaft and Distal Forearm Fractures in Children Aged 3 to 12 Years-A Prospective, Observational Study.

BACKGROUND: Although fracture displacement in children is easily treated by cast wedging, no data on pain associated with the procedure are available. We hypothesized that there is no clinically relevant difference in pain before and after cast wedging in children between 3 and 12 years of age. PATIENTS AND METHODS: This international, multicenter, prospective, observational study included 68 children (39 male, 29 female) aged 3 to 12 years (median age 8 years) with forearm fractures. Cast wedging was performed 5 to 10 days after the injury. Before starting the procedure, we administered a single oral dose of sodium metamizole (10 mg/kg body weight), and the children inhaled a nitrous oxide/oxygen mixture (50%/50%) during the wedging procedure. Pain was rated on a visual analog scale (VAS) 5 to 10 min before incision of the cast as well as 3 to 5 min and 30 min (maximum remembered pain) after inhalation stop. The degree of bending was judged either by the surgeon or was determined on the basis of first signs of pain expressed by the patient. We assessed the effectiveness of the procedure by obtaining X-ray images in two planes after 3 to 9 days. RESULTS: Among the 68 patients, median VAS score before cast wedging was 0. This increased to a score of 1 (p = 0.015) at 3 to 5 min after the procedure. Median VAS score for the maximum remembered pain measured after 30 min was 0. Median differences in angulation between proximal and distal bone fragments before and after the intervention were 0° (p < 0.0001) in the a.p. view and 8.4° (p < 0.0001) in the lateral view. CONCLUSION: Cast wedging improved the position of forearm fracture fragments at the expense of minimal short-term pain.

Laryngeal reflex responses in pediatric anesthesia.

Laryngeal and respiratory reflexes are vitally important defense mechanisms against foreign body aspiration, safeguarding airway patency, and ventilation. These highly preserved automatisms easily overrule external influences like willpower or (anesthetic) medication. Prevention and anticipation are, therefore, the essential strategies to avoid adverse events and damage, and treatment is most effective in the early stage of the reflex response. The physiology and pathophysiology of the various defensive reflexes as well as a comprehensive anesthetic approach to prevention and treatment are outlined in this review.

Dose evaluation of intravenous metamizole (dipyrone) in infants and children: a prospective population pharmacokinetic study.

PURPOSE: The prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants < 1 year. We aimed to assess the pharmacokinetics of the main metabolites of metamizole in children aged 3-72 months. METHODS: A single dose of 10 mg/kg metamizole was administered intravenously for postoperative analgesia. Pharmacokinetic samples were drawn at predefined time points. Pharmacokinetics of the main active metabolite 4-methylaminoantipyrine and three other metabolites was characterized by both non-compartmental and population pharmacokinetic analysis. AUC0-inf of 4-methylaminoantipyrine was calculated by non-compartmental analysis for two age cohorts (3-23 months, 2-6 years) and compared with the 80-125% range of adult dose-adjusted reference exposure (AUCref). Population pharmacokinetic analysis investigated age and weight dependency of the pharmacokinetics and optimal dosing strategies to achieve equivalent adult exposure. RESULTS: A total of 25 children aged 5 months-5.8 years (7.8-24.8 kg) with at least one concentration sample were included; 19 children had ≥ 5 predefined samples up to 10 h after metamizole dose administration. AUC0-inf of 4-methylaminoantipyrine in children 2-6 years was 29.9 mg/L/h (95% CI 23.4-38.2), significantly lower than AUCref (80-125% range 39.2-61.2 mg/L/h). AUC0-inf of 4-methylaminoantipyrine in infants < 2 years was 43.6 mg/L/h (95% CI 15.8-119.0), comparable with AUCref, while infants < 12 months showed increased exposure. Observed variability could be partially explained by covariates weight and age. CONCLUSIONS: Age-related changes in pharmacokinetics of 4-methylaminoantipyrine requires reduced weight-based IV dosing in infants < 1 year compared with infants and children up to 6 years (5 versus 10-20 mg/kg) to achieve equivalent adult exposure. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02660177 .

Severe Disruption of Water and Electrolyte Balance After Appendectomy: A Case Report.

Perioperative derangements of fluid and electrolyte homeostasis are rare complications in healthy children. Nonetheless, early diagnosis and treatment are mandatory to avoid a potentially life-threatening situation. However, the variety of underlying pathologies may prove to make accurate diagnosis challenging. This case report presents the management of an unexpected occurrence of a perioperative partial diabetes insipidus with massive fluid loss. Diagnostic and therapeutic procedures are discussed in the context of laboratory findings, and an overview of the existing literature is given. Finally, we emphasize that a multidisciplinary approach is most appropriate for diagnosis, accurate treatment, and follow-up of the patient.

A modified CO2/O2 Guedel airway improves capnographic accuracy compared with a CO2/O2 nasal cannula: An infant manikin study.

BACKGROUND: Capnography via a CO2/O2 nasal cannula is commonly used for respiratory monitoring during sedation. However, signal disturbances are frequently encountered, especially in young children. OBJECTIVE: Sampling ports placed closer to the trachea have been shown to result in improved signal quality. In a manikin model of a 6-month-old infant we compared capnography from a modified Guedel airway with a CO2 port located at the tip with that from a CO2/O2 nasal cannula. DESIGN: A comparison study using an artificial model of a breathing 6-month-old infant. SETTING: Department of Paediatrics, Inselspital Bern, Switzerland, from March 2016 to June 2016. MATERIAL: Modified CO2/O2 Guedel airway. INTERVENTIONS: Capnography using a modified CO2/O2 Guedel airway or a CO2/O2 nasal cannula was performed for tidal volumes of 20 to 80 ml (in steps of 20 ml), respiratory rates of 20 to 60 min (in steps of 10 min) and with different O2 flows (0 to 2 l min, in steps of 0.5 l). MAIN OUTCOME MEASURES: Comparison of differences between tracheal and device CO2. Secondary outcomes included the effect of various respiratory settings and O2 flows on the CO2 difference. RESULTS: The tracheal to device CO2 difference was significantly smaller when using a modified CO2/O2 Guedel airway vs. a CO2/O2 nasal cannula: Mean ±â€ŠSD, 16.8 ±â€Š4.9 vs. 24.1 ±â€Š5.9 mmHg, P less than 0.0001. An O2 flow of 0.5 to 2 l min did not influence the tracheal to device CO2 difference with the modified CO2/O2 Guedel airway in contrast to the CO2/O2 nasal cannula where there were significant differences (P < 0.0001). The effect of various tidal volumes and respiratory rates proved to be similar in both devices. CONCLUSION: Capnography traces derived from a sample port at the tip of a modified CO2/O2 Guedel airway were more accurate than those obtained from a CO2/O2 nasal cannula. TRIAL REGISTRATION: Not applicable.

Efficacy and Safety of Ibuprofen in Infants Aged Between 3 and 6 Months.

Ibuprofen is a non-steroidal anti-inflammatory drug frequently administered to children of various ages for relief of fever and pain and is approved as an over-the-counter medication in many countries worldwide. Although there are extensive data on its efficacy and safety in children and adults, there are divergent dosing recommendations for analgesia and treatment of fever in infants, especially in the age group between 3 and 6 months of age. In this article, we have assessed the safety and efficacy of ibuprofen use in infants in an attempt to find the optimal method of pain and fever management in this specific age group. Based on the current evidence, short-term use of ibuprofen is considered safe in infants older than 3 months of age having a body weight above 5-6 kg when special attention is given to the hydration of the patient. Ibuprofen should be prescribed based on body weight using a dose of 5-10 mg/kg. This dose can be administered 3-4 times a day resulting in a maximum total daily dose of 30-40 mg/kg. The rectal route has been shown to be less reliable because of erratic absorption, especially in young infants. Since most efficacy and safety data have been derived from trials in infants with fever, future studies should focus on the efficacy of ibuprofen in young infants with pain.

Impact of high concentrations of sevoflurane on laryngeal reflex responses.

BACKGROUND: Exaggerated defensive upper airway reflexes, particularly laryngospasm, may cause hypoxemic damage, especially in children. General clinical experience suggests that laryngeal reflex responses are more common under light levels of anesthesia, and previous clinical studies have shown an inverse correlation between laryngeal responsiveness and depth of hypnosis. However, this seems to be less obvious in children anesthetized with sevoflurane. The aim of this study was to assess the impact of high concentrations of sevoflurane on laryngeal and respiratory reflex responses in spontaneously breathing children. Accordingly, we tested the hypothesis that laryngeal and respiratory reflex responses were completely suppressed in spontaneously breathing children when anesthetized with sevoflurane 4.7% (=MACED95Intubation ) as compared with sevoflurane 2.5% (=1 MAC). METHODS: In this prospective observational study, we tested the hypothesis that the incidence of laryngospasm evoked by laryngeal stimulation is diminished under high concentrations of sevoflurane. Following Ethics approval, trial registration, and informed consent, 40 children (3-7 years) scheduled for elective surgery participated in the trial. All children received sevoflurane 2.5% (1 MAC) and 4.7% (ED95Intubation ) in random order with 5-min equilibration between the states. Under both conditions, distilled water was sprayed under bronchoscopic view onto the larynx. Potential laryngeal and respiratory reflex responses were assessed offline by a blinded reviewer. RESULTS: Laryngospasm (episodes lasting >10 s) occurred in 12/38 (32%) of the patients anesthetized with sevoflurane 2.5%, vs 7/38 (18%) in those anesthetized with sevoflurane 4.7% (difference: OR 3.5; 95% CI [0.72-16.84], P = 0.18). All other reflex responses (coughing, expiration reflexes, and spasmodic panting) were infrequent and were similar among the examined concentrations. CONCLUSION: Against our hypothesis, laryngospasm could still be observed in 18% of children under the higher concentration of sevoflurane (4.7%, ED95Intubation ).

Topical Lidocaine Does Not Exaggerate Laryngomalacia in Infants During Flexible Bronchoscopy Under Propofol Anesthesia.

BACKGROUND: Topical lidocaine has been found to result in overestimation of the severity of laryngomalacia in infants undergoing flexible bronchoscopy under conscious sedation with midazolam and nalbuphine. This effect has never been confirmed and may depend on the level of sedation and the drugs used. We assessed the effect of topical lidocaine on laryngomalacia in infants undergoing flexible bronchoscopy under general anesthesia with propofol. METHODS: Thirteen infants with congenital stridor referred to diagnostic flexible video-bronchoscopy were studied under propofol anesthesia before and 3 minutes after topical lidocaine administration to the larynx at a dose of 3 mg/kg body weight. Laryngomalacia was scored using 60 seconds video recordings of the larynx before and after lidocaine administration in random order by 2 independent blinded observers using the previously described arytenoid score (AS), epiglottis score (ES), and the total score (TS=AS+ES). RESULTS: No significant differences in AS, ES, and laryngomalacia score were found between the prelidocaine and postlidocaine assessments by the 2 raters. The intraclass correlation coefficients were 0.995 (95% confidence interval, 0.986-0.998) and 0.975 (0.930-0.991) and 0.989 (0.971-996) for AS, ES, and TS, respectively. CONCLUSIONS: The assessment of laryngomalacia is not affected by topical lidocaine under propofol anesthesia. The lidocaine effect on laryngomalacia may vary depending on the medication regime used and the depth of procedural sedation.

Surgical treatment of craniosynostosis in infants: open vs closed repair.

PURPOSE OF REVIEW: Correction of craniosynostosis may require extensive surgical interventions with related intra and postoperative complications especially hemorrhage. To reduce the intervention's impact and associated complications, less invasive surgical alternatives have evolved. The present review comprehensively summarizes surgical techniques, perioperative anesthesia management, success rates, complications, the results of outcome evaluations, and predictors of intra and postoperative complications. RECENT FINDINGS: Recent evaluations suggest that less invasive methods represent valuable techniques with comparable cosmetic and volumetric results but reduced overall impact and complications. Furthermore, risk stratification based on predictors might optimize safety and guide decision-making concerning the required level of postoperative clinical care. SUMMARY: Neuroendoscopic techniques, designed to minimize surgical incision, dissection, and blood loss, are becoming efficacious and valuable alternative therapeutic options reducing the need for fluid replacement and invasive hemodynamic monitoring. Since hemorrhage represents the most important complication in open craniosynostosis repair, prevention strategies such as the use of tranexamic acid should be considered. Sufficient correction of entailed coagulopathies is crucial.

Assessment of three placement techniques for individualized positioning of the tip of the tracheal tube in children under the age of 4 years.

BACKGROUND: Accurate positioning of the tip of the tracheal tube (tube tip) is challenging in young children. Prevalent clinical methods include placement of intubation depth marks, palpation of the tube cuff in the suprasternal notch, or deliberate mainstem intubation with subsequent withdrawal. To compare the predictability of tube tip positions, variability of the resulting positions in relation to the carina was determined applying the three techniques in each patient. METHODS: In 68 healthy children aged ≤4 years, intubation was performed with an age-adapted, high-volume low-pressure cuffed tube adjusting the imprinted depth mark to the level of the vocal cords. The tube tip-to-carina distance was measured endoscopically. Thereafter, placements using (I) cuff palpation in the suprasternal notch and (II) auscultation to determine change in breath sounds during withdrawal after bronchial mainstem intubation were completed in random order. RESULTS: Tube tip position above the carina was higher when using depth marks (mean = 36.8 mm) compared with cuff palpation in the suprasternal notch (mean = 19.0 mm). Variability, expressed as sd, was lowest with the mainstem intubation technique (5.2 mm) followed by the cuff palpation (7.4 mm) and the depth mark technique (11.2 mm) (P < 0.005). CONCLUSION: Auscultation after deliberate mainstem intubation and cuff palpation resulted in a tube tip position above the carina that was shorter and more predictable than placement of the tube using depth markings.

Endoscopic pediatric neurosurgery: implications for anesthesia.

Endoscopic surgery is increasingly utilized in neurosurgery for all pediatric age groups. Endoscopic intraventricular neurosurgery represents a unique approach to intracranial pathology but may cause a unique set of limitations and potential complications. Important endoscopic neurosurgical techniques and their indications, perioperative anesthesia management, complications, and success rates are reviewed with special emphasis on endoscopic third ventriculostomy and endoscopic-assisted strip craniectomy in early infancy. Despite encouraging short- and long-term results of early pediatric endoscopic neurosurgery, multicenter randomized studies will be needed to further determine safety and the effect on cognitive development and quality of life.

The effect of deep vs. awake extubation on respiratory complications in high-risk children undergoing adenotonsillectomy: a randomised controlled trial.

CONTEXT: There is ongoing debate regarding the optimal timing for tracheal extubation in children at increased risk of perioperative respiratory adverse events, particularly following adenotonsillectomy. OBJECTIVE: To assess the occurrence of perioperative respiratory adverse events in children undergoing elective adenotonsillectomy extubated under deep anaesthesia or when fully awake. DESIGN: Prospective, randomised controlled trial. SETTING: Tertiary paediatric hospital. PATIENTS: One hundred children (<16 years), with at least one risk factor for perioperative respiratory adverse events (current or recent upper respiratory tract infection in the past 2 weeks, eczema, wheezing in the past 12 months, dry nocturnal cough, wheezing on exercise, family history of asthma, eczema or hay fever as well as passive smoking). INTERVENTION: Deep or awake extubation. MAIN OUTCOME MEASURE: The occurrence of perioperative respiratory adverse events (laryngospasm, bronchospasm, persistent coughing, airway obstruction, desaturation <95%). RESULTS: There were no differences between the two groups with regard to age, medical and surgical parameters. The overall incidence of complications did not differ between the two groups; tracheal extubation in fully awake children was associated with a greater incidence of persistent coughing (60 vs. 35%, P = 0.028), whereas the incidence of airway obstruction relieved by simple airway manoeuvres in children extubated while deeply anaesthetised was greater (26 vs. 8%, P = 0.03). There was no difference in the incidence of oxygen desaturation lasting more than 10 s. CONCLUSION: There was no difference in the overall incidence of perioperative respiratory adverse events. Both extubation techniques may be used in high-risk children undergoing adenotonsillectomy provided that the child is monitored closely in the postoperative period. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12609000387224.